Public Health Nutrition: 14(4), 709715 doi:10.

1017/S1368980010001783

The effects of vitamin C supplementation on incident and

progressive knee osteoarthritis: a longitudinal study
Jennifer Peregoy1 and Frances Vaughn Wilder2,*
1
Department of Epidemiology, College of Public Health, University of South Florida, Clearwater, FL, USA:
2
Department of Epidemiology, College of Public Health, The Arthritis Research Institute of America, University of
South Florida, 300 S. Duncan Avenue Suite #188, Clearwater, FL 33755, USA

Submitted 3 July 2009: Accepted 13 May 2010: First published online 16 August 2010

Abstract
Objective: To evaluate the association between vitamin C supplementation and
the incidence and progression of radiographic knee osteoarthritis (OA).
Design: Prospective cohort study.
Setting: Clearwater Osteoarthritis Study (COS): (1988 to the present) a long-
itudinal study.
Subjects: Male and female COS participants aged 40 years and above (n 1023).
The study exposure was the participants self-reported history of vitamin C supple-
mentation. The participants underwent biennial, sequential knee radiographs, which
were assessed using the KellgrenLawrence ordinal scale to determine evidence of the
study 2 outcomes: incident radiographic knee OA (RKOA) and progression of RKOA.
Results: Individuals without baseline knee OA who self-reported vitamin C supple-
ment usage were 11 % less likely to develop knee OA than were those individuals
who self-reported no vitamin C supplement usage (risk ratio (RR) 5 0?89, 95 % CI
0?85, 0?93). Among those participants with RKOA at baseline, vitamin C supplement
usage did not demonstrate an association with RKOA progression (RR 5 0?94, 95 %
CI 0?79, 1?22).
Conclusions: In the present prospective cohort study, we found no evidence to
Keywords
support a protective role of vitamin C in the progression of knee OA. However, after
Knee osteoarthritis
controlling for confounding variables, these data suggest that vitamin C supple- Epidemiology
mentation may indeed be beneficial in preventing incident knee OA. Given the Incidence
massive public health burden of OA, the use of a simple, widely available and Vitamin C
inexpensive supplement to potentially reduce the impact of this disease merits Ascorbic acid
further consideration. Antioxidant

Damage caused by free radicals has long been thought to
be pathogenic and they play an important role in the pro-
gression of many chronic diseases, including CVD and
osteoarthritis (OA)(16). Free radicals are unstable, reactive
molecules with unpaired electrons that are primarily created
via the aerobic metabolism and the immune response
to antigen. In the absence of sufficient antioxidants, free
radicals can wreak havoc on neighbouring cells, causing
cytotoxicity and cellular damage(7). In fact, although OA
is defined as a non-inflammatory arthropathy, there is
evidence that pro-inflammatory molecules play an impor-
tant role as mediators in the pathogenesis of OA(8,9).
Thus, there is significant scientific interest in studying the
efficacy of nutritional therapeutics to combat such chronic
diseases, specifically dietary antioxidants such as vitamin C.
In addition to its antioxidant capacity, vitamin C is critical
to bone health, acting as an electron donor in the synthesis
of type II collagen(46). It is also a sulfate carrier in glyco-
saminoglycan synthesis. This may be relevant to OA
aetiology because the depletion of sulfated proteoglycans
from the articular cartilage extracellular matrix is one of the
earliest expressions of OA, eventually resulting in cartilage
degeneration(6). Vitamin C deficiency may therefore be a
risk factor in the development of OA, leading to the logical
possibility of using vitamin C supplementation for primary
prevention or as a therapeutic intervention for OA. The
present study followed a group of participants free of
radiographic knee OA (RKOA) to quantify the role of
vitamin C supplement usage in incident RKOA. In addition,
among a group of participants with RKOA at baseline, we
examined the relationship between vitamin C supplement
usage and RKOA progression.
Methods
The study hypotheses were: (i) among those without
RKOA at study baseline, the likelihood of developing

*Corresponding author: Email fwilder@preventarthritis.org r The Authors 2010

710
RKOA is lower among those participants reporting
vitamin C supplement usage than among those who report
no vitamin C supplement usage; and (ii) among those
with RKOA at baseline, the likelihood of RKOA progres-
sion is lower among those participants reporting vitamin
C supplement usage than among those who report no
vitamin C supplement usage. The two study outcomes
were RKOA incidence and RKOA progression. The study
exposure, vitamin C supplementation, was defined as the
cumulative number of years of self-reported vitamin C
supplement usage since study enrolment.
Subjects
The Clearwater Osteoarthritis Study (COS), initiated by
The Arthritis Research Institute of America in 1988, is an
on-going community-based, prospective cohort study with
over 3700 participants (aged .40 years). The research
objective of the COS is to identify the major risk factors for
the development and progression of OA and to differentiate
risk factors for localised and generalised primary OA.
Data are collected from study participants biennially, and
include demographic, historical, clinical and radiological
information. COS volunteer recruitment is conducted using
a variety of methods, including invitational letters, television
and radio announcements, newspaper articles publicising
the COS study, articles posted in community organisations
bulletins, as well as seminars held at community clubs
and organisations. To ensure a representative sample that
includes younger participants who are more likely to be free
of OA, recruitment efforts were used to encourage partici-
pation by employees of the Pinellas County School System,
the City of Clearwater and Pinellas County Inc.
Data collection
During the initial visit, a detailed study description was
given to the participant, followed by a screening ques-
tionnaire to determine eligibility based on predetermined
inclusion/exclusion criteria. Exclusion criteria were limited
to individuals with self-reported rheumatoid arthritis
or variants (lupus erythematosus, ankylosing spondylitis,
etc.), gout, disabling neuralgic disease, confined to a
wheelchair or mentally incompetent. Once eligibility was
established, informed consent was obtained before data
collection. All eligible, voluntary participants completed
the COS history questionnaire and underwent a physical
examination. This examination included radiographs
of four sites including the anteriorposterior weight-
bearing knee, taken by a licensed X-ray technician using
standardised exposure techniques. Study participants
were re-evaluated biennially, updating the history ques-
tionnaire and the clinical examination information.
Radiographic measurement
Radiographs were interpreted by a board-certified radiologist,
blinded to the individual study participants status. Using the
KellgrenLawrence ordinal scale(10), knee OA cases were
J Peregoy and FV Wilder
defined as those with grades .2, whereas those with grades
0 or 1 were considered disease-free. An incident case was
defined as a participant who was free of RKOA in both
knees at study baseline, but developed RKOA in either one
or both knees during the observation period. A progression
case was defined as a study participant (with uni- or bilat-
eral RKOA at baseline) who experienced the outcome of
RKOA progression (of $1 grade) during the follow-up
period. Quality control measures were taken to ensure the
validity of the radiographic assessments. Every tenth parti-
cipants assembled radiographs were independently inter-
preted by a non-affiliated radiologist (blinded to initial
reading results), allowing for the quantification of inter-
observer variability. This was calculated using the k coeffi-
cient, measuring the extent of reader agreement above than
due to chance alone(11). Inter-reader reliability by a second
radiologist reflected 93 % agreement (k 5 0?85).
Questionnaire
Information regarding the history of the participants vita-
min C supplement usage was collected using the COS
history questionnaire. Participants who indicated vitamin C
supplement usage were further queried with Age started?
and Age stopped? The COS database was being explored
for its nutrition-related variables. A recently published
COS study suggested a potentially protective relationship
between multivitamin usage and the risk of the develop-
ment and progression of OA(12). To best assess solely
the role of vitamin C, all participants who reported a history
of multivitamin usage were excluded from the present
analyses.
In an effort to identify and control for potential con-
founders, several variables associated with RKOA and
vitamin C supplementation were investigated. Potential
confounders investigated were age, gender, baseline BMI,
history of knee injury, exercise status and total years
of vitamin C supplement usage before study baseline.
Participants history of knee injury was a self-reported yes/no
variable. The questionnaire asked Have you ever been
told by a doctor that you have a cracked, fractured,
broken or dislocated bone? If the participant answered
yes, they were asked to select from a list of body sites (e.g.
knee) to indicate where they sustained an injury. Exerci-
sers were defined as those participants who self-reported
an exercise frequency of at least three times weekly (for
minimum of 20 min per session). For the present analyses,
confounders were defined as any factors associated with
the outcome (RKOA incidence/RKOA progression) and
differentially distributed by exposure status (vitamin C
supplementation since study enrolment). Baseline BMI,
age and prior years of vitamin C supplement usage were
included in the adjusted analysis as continuous variables.
Statistical analyses
With 866 participants classified as eligible for developing
RKOA, the present study had an 80 % power to detect a
Radiographic osteoarthritis and vitamin C
20 % or greater difference in RKOA incidence by vitamin C
supplement usage. Although the study of RKOA pro-
gression was limited to 157 participants, this sample size
was also sufficient to allow for 80 % power to detect a
Clearwater Osteoarthritis
Study participants
(n 3642)
No history of
knee joint replacement
(n 3602)
711
20 % difference in RKOA progression by vitamin C status,
if indeed a difference existed (two-tailed; a 5 0?05)(13).
Given the unequal follow-up times and censored par-
ticipants inherent in a cohort study design, the Cox pro-
portional hazards model was applied(14,15) to quantify the
relationship between vitamin C supplement usage and
RKOA while simultaneously controlling for the influence
of other factors discussed above. The Cox regression
model was also used to calculate the unadjusted risk
ratios (RR), with vitamin C supplementation as the sole
independent variable. The study observation period was
the interval between study enrolment and either (i) the
development of RKOA; (ii) study withdrawal; or (iii)
censoring. Results were expressed as RR (hazard ratios),
along with the corresponding 95 % CI and P values.
P , 0?05 was considered statistically significant. The data
analyses were conducted using the SAS statistical software
package version 9?13 (SAS Institute, Cary, NC, USA),
specifically applying PROC PHREG(16).

Results
No history of multivitamin
supplement usage The final sample size was 1023. Figure 1 displays the
(n 1543)
participant selection process. Of the 866 participants free
of RKOA at baseline, 341 (39 %) developed RKOA during
the observation period. Among the 157 study participants
with RKOA at baseline, fifty-one (32 %) experienced
RKOA progression during the observation period. The mean
period of observation among those with and without base-
Complete data for key variables line RKOA was 7?5 (SD 5?3) and 6?1 (SD 4?4) years, respec-
(e.g. OA status, vitamin usage)
(n 1362)
tively. The average time between physical examinations
for RKOA progression and incident cohorts was 2?08 (SD
0?39) and 2?12 (SD 0?42) years, respectively. Table 1
summarises study sample characteristics for the RKOA
incidence and progression analyses.
The unadjusted RR, generated using Coxs regression
with vitamin C supplement usage as the sole independent
Not lost to follow-up
(n 1023) variable, quantified the association between vitamin C
supplement usage and incident RKOA. These data indi-
cated that those individuals reporting vitamin C supple-
Fig. 1 Sample selection from the Clearwater Osteoarthritis ment usage were 7 % less likely to develop RKOA than
Study (n 1023). OA, osteoarthritis those individuals who reported no vitamin C supplement

Table 1 Study sample baseline characteristics (by radiographic knee osteoarthritis status)

Incidence analyses Progression analyses

(n 866) (n 157)

n % n %

Female 553 63?9 88 56?1

Knee injury history (yes) 390 45?0 76 48?4
Exercise status (yes) 291 37?9 49 36?8

Average SD Average SD

BMI (kg/m2) 25?6 4?0 28?1 5?6

Age (years) 61?1 10?6 66?5 8?7
Total years of vitamin C supplement usage before study baseline 3?2 9?1 2?8 9?7
712
Table 2 Radiographic knee osteoarthritis and vitamin C supple-
ment usage
Unadjusted Adjusted-
RR 95 % CI RR
Incidence 0?93 0?89, 0?96* 0?89
Progression 0?91 0?79, 1?04 0?94
*P value , 0?0001.
- Adjusted for BMI, gender, age, knee injury history, exercise and vitamin C
supplement usage before study baseline.
usage (RR 5 0?93, 95 % CI 0?89, 0?96; Table 2). Adjusted
analyses simultaneously considered the possible effects
of baseline BMI, gender, age, knee injury history, exercise
status and total years of vitamin C supplement usage
before study baseline. The adjusted association between
vitamin C supplement usage and incident RKOA demons-
trated that those individuals reporting vitamin C supple-
ment usage were 11 % less likely to develop RKOA than
those individuals who reported no vitamin C supplement
usage (RR 5 0?89, 95 % CI 85, 0?93; Table 2).
Among those participants with baseline RKOA, the un-
adjusted RR quantified the association between vitamin C
supplement usage and the subsequent progression of
RKOA. These data did not demonstrate a statistically
significant relationship between vitamin C supplement
usage and RKOA progression (RR 5 0?91, 95 % CI 0?79,
1?04, P value 5 0?15; Table 2). The adjusted risk estimate
assessing vitamin C supplement usage and RKOA pro-
gression did not indicate a relationship between vitamin
C supplement usage and RKOA progression (RR 5 0?94,
95 % CI 0?79, 1?12, P value 5 0?48; Table 2).
Discussion
This epidemiological investigation demonstrated an
association between vitamin C supplement usage and
a reduced incidence of RKOA. These findings are sup-
ported by a cross-sectional study conducted in 2007,
examining the effect of antioxidant intake on knee carti-
lage and bone in healthy individuals (n 293)(17). Anti-
oxidant intake was estimated from a baseline FFQ. MRI of
the knee was taken at baseline and again at 10 years.
Wang et al.(17) found vitamin C intake to be associated
with a 50 % risk reduction of bone marrow lesions (OR 5
0?50, 95 % CI 0?29, 0?87, P 5 0?01) and inversely asso-
ciated with tibial plateau bone area (b 5 235?5 %, 95 %
CI 5 268?8, 22?3, P 5 0?04), both of which are involved
in the pathogenesis of knee OA. Increased vitamin C
intake has also been shown to exhibit a slight chon-
droprotective effect (P 5 0?08) on the development of
spontaneous lesions in guinea pigs, with no such effect
on the progression of surgically induced OA(18). The
findings of Kurz et al.(4) demonstrated a similar positive
association between antioxidant supplements (vitamins A,
J Peregoy and FV Wilder
C, E, B6, B2 and selenium) and reduced incidence of knee
OA in OA-prone mice. It was found that the supple-
mented diet induced a 1?5-fold increase in enzymatic
antioxidant activity, with the authors concluding that the
95 % CI
selected combination of vitamins and selenium dimin-
0?85, 0?93* ished the mechanical induction of OA in mice. However,
0?79, 1?12
given the multivitamin supplementation strategy used in
that study, it is difficult to conclude which of these
nutrients may have had the largest influence or whether
synergistic effects played a role.
However, among those with RKOA, the present study
found no statistically significant association between
vitamin C supplement usage and reduced progression of
RKOA. Some previously published, related clinical studies
have reported opposite findings. In the Framingham
Osteoarthritis Study, a threefold risk reduction in OA
progression was observed in both the middle tertile
(OR 5 0?3, 95 % CI 0?1, 0?8) and highest tertile (OR 5 0?3,
95 % CI 0?1, 0?6) of vitamin C intake, yet no association
was found between vitamin C and incident OA(5). McA-
lindon et al.(5) also noted that those with the highest
vitamin C intake experienced a reduced risk of develop-
ing knee pain (OR 5 0?3, 95 % CI 0?1, 0?8). Reduction in
OA knee pain associated with vitamin C supplementation
has been established in several clinical investigations,
such as those recently conducted by Jensen et al.(19) and
Baker et al.(20). Although the Framingham Osteoarthritis
Study was rigorous in its design and execution, the study
used a relatively small sample size (n 81 for incident OA;
n 68 for progressive OA). Similar results demonstrated in
the MOST study found that those with the lowest serum
vitamin C concentration were at a twofold greater risk
of further OA progression as compared to those in the
highest quartile (OR 5 2?12, 95 % CI 1?30, 3?46, P 5 0?003),
yet found no statistically significant association between
serum vitamin C and knee OA incidence (n 156 for incident
OA; n 408 for progressive OA)(21).
Vitamin C status has been shown to influence the
progression of OA in animal models as well. In a study
conducted by Schwartz et al.(22), guinea pigs were sup-
plemented with either low or high doses (150 mg/d)
of ascorbate before surgically inducing knee OA. The
animals on low dose were marked by more severe
pathological changes than those seen in high-dose ani-
mals. The high-dose animals demonstrated higher carti-
lage retention in their normal joints, suggesting that the
vitamin C stimulated additional collagen production.
Schwartz et al.(22) concluded that high doses of ascorbate
have a protective effect on the severity of surgically
induced knee OA in guinea pigs. Our findings failed to
support such an association among participants with
RKOA and self-reported vitamin C status. Hill and Bird(23)
also failed to report an association between selenium
ACE supplementation and knee OA outcomes (pain, stiff-
ness and radiographic evidence of disease progression).
Although this was a rigorous 6-month, double-blind
Radiographic osteoarthritis and vitamin C
placebo-controlled trial, study limitations (including trace
amounts of selenium found in the placebo), as well as
low power due to small sample size (n 30) should be
considered.
In contradiction to all other published findings, a 2004
study conducted on guinea pigs observed a dose-dependent,
positive association between ascorbic acid supplementation
and the severity of spontaneous OA(24). In addition, Kraus
et al.(24) noted a correlation between the knee joint histolo-
gical severity scores and plasma ascorbate concentration
(r 5 0?38, P 5 0?01) and concluded that osteoarthritic patients
should not consume above the Recommended Daily Value
for vitamin C. The present study highlights the complexity of
the relationship between the pathogenesis of OA and dietary
antioxidant consumption and underscores the need for
related, rigorous clinical research investigations.
The association demonstrated between vitamin C
supplementation and the reduced risk of incident RKOA
in our study, while inconsistent with data from some
published studies, is biologically plausible given the
current understanding of the physiological effects of
vitamin C intake on bone health and the natural history of
OA. It has been commonly hypothesised that mechanical
stress on the joints may lead to free radical accumulation
and subsequent articular cartilage degradation, leading to
OA symptoms(4,25). This presents the possibility that the
consumption of antioxidants may reduce the incidence of
OA by preventing or minimising the occurrence of oxi-
dative cartilage damage. Evidence from both in vitro and
animal model studies supports this hypothesis.
The chondrocyte in normal human cartilage maintains a
metabolic homeostasis, balancing between anabolism and
catabolism of the extracellular matrix. However, in chon-
drocytes of OA-affected individuals, this balance is skewed
in favour of catabolism, resulting in matrix degradation
and eventual loss of the articular cartilage that leads to
OA symptoms and progression(26,27). Thus, a major focus
of OA research has been on the mechanism of the
chondrocyte in the OA disease pathway. The findings of
Yudoh et al.(28) demonstrated that oxidative stress indu-
ces genomic instability and dysfunction of human chon-
drocytes in OA cartilage, with ascorbic acid mitigating this
effect. This suggests that oxidative stress may indeed play
a significant role in the cartilage degradation associated
with the development of OA, with implications that
antioxidants such as vitamin C may reduce this risk.
Similarly, vitamin C supplementation has been demon-
strated to reduce in vitro chondrocyte degeneration,
marked by reduced morphological degradation and
higher collagen content, after static loading(29).
Cartilage metabolism, a step in the OA disease path-
way, has been demonstrated to be directly affected by
vitamin C status in animal models. Peterkovsky et al.(30)
observed decreased cartilage collagen synthesis in vitamin
C-deficient guinea pigs, while conversely, the addition of
ascorbate to guinea pig articular cartilage explants has
713
been shown to increase the synthesis of collagen and
aggrecan(31). Although classic signs of inflammation are
absent in OA (e.g. neutrophils in synovial fluid), there
is significant evidence that suggests that inflammatory
molecules may be important mediators in the OA disease
pathway(27,32). For instance, inflammatory cytokines such
as IL-1 have been found in the synovial fluid of OA
patients and are known to stimulate catabolic processes
such as the synthesis of proteolytic enzymes. Research
has shown that chondrocytes of OA-afflicted individuals
exhibit enhanced expression of pro-inflammatory cyto-
kines and inducible NO synthase, the molecule that sti-
mulates the production of NO, a strong oxidising
agent(27). These inflammatory cytokines have been linked
to the inhibition of cartilage proteoglycan and collagen
synthesis, as well as chondrocyte apoptosis(27,32). If
indeed these autocrine/paracrine inflammatory pathways
play a pathogenic role in the development or progression
of OA, it is reasonable to believe that antioxidant sup-
plements such as vitamin C may prove to be a powerful
tool in the primary or secondary prevention of this disease.
Vitamin C as an anti-inflammatory molecule is virtually
unrivalled in its potency. Although studies conducted on the
role of vitamin C in OA pathology have yielded conflicting
results, it continues to be an active area of research that
merits further investigation.
Study strengths and limitations
The present studys prospective cohort design is able to
clearly establish the temporal relationship between vitamin
C supplement usage and the subsequent development of
RKOA. A strength of the present study is the collection of
serial radiographs for all participants beginning at study
entry, allowing us to determine pre-existing RKOA disease
status among the study participants. Loss to follow-up
is always of concern in any prospective cohort design.
Differences by selected characteristics between those parti-
cipants who were lost to follow-up and those who were
not lost were examined (Table 3). Overall, it can be seen
that the two groups, lost and retained, had similar baseline
characteristics. There were no significant differences
between the two groups by age, sex, BMI, knee injury status
or exercise status. However, the total years of vitamin C
supplement usage before study baseline among the parti-
cipants lost to follow-up was half that of the retained
participants. Although our adjusted analyses included this
factor, it is possible that the study results may have been
biased away from the null.
A study limitation is the self-reported nature of the
exposure, vitamin C supplement usage. Whenever self-
reported data are collected, there exists the possibility of
misclassification. Yet the prospective cohort design with
biennial examinations minimised the risk of misclassifica-
tion due to recall bias. In addition, ascribing an association
of vitamins and better health to a causal path may be
fraught with problems. Persons who regularly take vitamin
714 J Peregoy and FV Wilder
Table 3 Evaluation of losses to follow-up by baseline characteristics (vitamin C supplement usage and radiographic knee OA)

Incidence analyses Progression analyses

Retained Lost Retained Lost

(n 866) (n 272) (n 157) (n 67)

Female 63?9 63?2 56?1 59?7

Knee injury history (yes) 45?0 50?0 48?4 46?3
Exercise status (yes) 37?9 35?7 36?8 37?9
Baseline knee OA score 5 2 N/A N/A 65?0 50?8
Baseline knee OA score 5 3 N/A N/A 21?0 23?9
BMI (kg/m2) 25?6 25?7 28?1 29?6
Age (years) 61?1 62?5 66?5 66?5
Total years of vitamin C supplement usage before study baseline 3?2 1?6 2?8 1?4

OA, osteoarthritis; N/A, not applicable.

C may routinely demonstrate health choices that impact
their predisposition to OA. They may be more concerned
with their health compared with persons who do not take
vitamin C. Therefore, although a causal interpretation
cannot be ruled out, it is by no means proven. As with
any epidemiological study, confounding poses a threat to
validity. Yet, appropriate measures were taken by applying
restrictive inclusion/exclusion criteria and conducting
multivariate analyses to address potential bias. The statis-
tical power afforded by the large sample size is a strength of
the present study. Although employing smaller sample
sizes, related previously conducted studies provided the
justification for our research. Our study builds on those
findings. In addition, the inter-reader variability of the
radiographic assessments was quite low, as demonstrated
by the high k value. There is some controversy about OA
diagnoses (e.g. symptomatic, radiographic, weight-bearing
status, etc.). To assess OA incidence and progression, the
present study employed the KellgrenLawrence scale, a
fairly common approach with films read blindly using
a standardised technique. Given that the Kellgren
Lawrence composite score relies heavily on osteophytes,
it may be useful to examine the development of osteo-
phytes and joint space narrowing separately to further
elucidate the mechanism of action of vitamin C. The
feasibility of the necessary research protocol modifica-
tions is being investigated to include such an assessment
for future COS radiographic examinations.
In conclusion, new efforts to prevent the incidence and
progression of radiographic OA may include strategies
aimed at reducing oxidative damage in cartilage, thought
to promote this disease. OA, the most common joint
disease and a leading cause of disability, affects more
than 27 million persons in the USA(33). Vitamin C sup-
plementation may very well be an effective strategy to
combat this growing public health problem. However,
there is at present a lack of substantial evidence to support
this theory. There are strong inconsistencies found in
both the study designs and outcomes, rendering it diffi-
cult to compare results across studies. The acceptable and
most effective dosing range of vitamin C is still con-
troversial, but recent studies have found that doses of up
to 2000 mg/d are safe for most adults(33,34). Clinicians may
want to consider recommending vitamin C supplements
to those at greatest risk for OA, as it has been shown to
be safe within the normal dosing range and may offer
additional health benefits beyond the hypothesised pro-
tection against OA. Multiple laboratory and clinical
studies have shown promising results for the protective
effect of vitamin C intake on the course of OA, including
disease incidence, progression and symptomatology. Yet
the heterogeneity of the related study findings provides
evidence that further clinical studies are required to
carefully investigate the safety and efficacy of the use of
vitamin C in preventing or slowing the progression of OA.
Acknowledgements
The institutes research is supported by private funding.
The authors have no conflicts of interest to declare. J.P.
contributed to the literature review, data interpretation,
manuscript writing and manuscript preparation; F.V.W.
contributed to the study design, computer programming,
data interpretation and manuscript writing.
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